A paradigm shift in the prevention and diagnosis of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a widespread disease with only 50%-60% 5-year survival. Individuals with potentially malignant precursor lesions are at high risk. METHODS: Survival could be increased by effective, affordable, and simple screening methods, along with a shift from incisional tissue biopsies to non-invasive brush biopsies for cytology diagnosis, which are easy to perform in primary care. Along with the explainable, fast, and objective artificial intelligence characterisation of cells through deep learning, an easy-to-use, rapid, and cost-effective methodology for finding high-risk lesions is achievable. The collection of cytology samples offers the further opportunity of explorative genomic analysis. RESULTS: Our prospective multicentre study of patients with leukoplakia yields a vast number of oral keratinocytes. In addition to cytopathological analysis, whole-slide imaging and the training of deep neural networks, samples are analysed according to a single-cell RNA sequencing protocol, enabling mapping of the entire keratinocyte transcriptome. Mapping the changes in the genetic profile, based on mRNA expression, facilitates the identification of biomarkers that predict cancer transformation. CONCLUSION: This position paper highlights non-invasive methods for identifying patients with oral mucosal lesions at risk of malignant transformation. Reliable non-invasive methods for screening at-risk individuals bring the early diagnosis of OSCC within reach. The use of biomarkers to decide on a targeted therapy is most likely to improve the outcome. With the large-scale collection of samples following patients over time, combined with genomic analysis and modern machine-learning-based approaches for finding patterns in data, this path holds great promise.

Minding the gap and the value of metrics: Count of working pharmacists in the United States.

BACKGROUND: The Bureau of Labor Statistics (BLS) uses a single Standard Occupational Classification (SOC) code (29-1051) that reflects a traditional definition of pharmacist job functions. Pharmacists working in nontraditional roles would be categorized under other SOC codes and not included in the BLS pharmacist count. Knowing the magnitude of how many working pharmacists may not be included in the BLS pharmacist count would help determine whether the gap is a minor margin of error or a significant problem affecting pharmacist workforce projections. OBJECTIVES: The primary objective of this paper was to estimate the gap between the number of possibly working pharmacists and the BLS pharmacist count in 2019. A secondary objective was to examine BLS pharmacist counts in nontraditional roles and compare with published industry data. METHODS: The annual number of individuals receiving their first professional pharmacy degree from 1965 to 2019 (55 graduation cohorts) was adjusted using the expected survival rate to 2019 by age and gender and workforce participation rate in 2019 for pharmacists for each cohort and then summed across cohorts. Data sources included Accreditation Council for Pharmacy Education, U.S. Vital Statistics reports, and American Consumer Survey. One-way and scenario-based sensitivity analyses were conducted to vary professional occupation mortality advantage and pharmacist workforce participation rate assumptions. RESULTS: Based on the number of individuals receiving their first professional pharmacy degree between 1965 and 2019 (442,409), there were 356,998 possibly working pharmacists in 2019. This value indicates 45,798 more pharmacists (15%) may have been working in 2019 than the 311,200 employee pharmacists reported by BLS for 2019. A gap of 8000 to 46,000 more working pharmacists (3%-15%) versus BLS persisted after sensitivity analyses. CONCLUSION: The magnitude of possibly working pharmacists not included in BLS counts warrants further consideration of current pharmacist job projections, methods, and metrics to improve future projections and monitoring of the pharmacist labor force.

Dental hygienists and dentists as providers of brush biopsies for oral mucosa screening.

BACKGROUND: Oral cancer is a severe and potentially fatal disease usually starting in the squamous epithelium lining the oral cavity. Together with oropharyngeal carcinoma, it is the fifth to sixth most common malignancy worldwide. To limit the increase in the global oral cancer incidence over the past two decades, the World Health Assembly adopted a resolution urging member states to integrate preventive measures such as engagement and training of dental personnel in screening, early diagnosis, and treatment into their national cancer control programs. AIM: The aim of this study was to investigate if dental hygienists (DHs) and dentists (Ds) in general dental practice care can be entrusted to perform brush sampling of oral potentially malignant disorders (OPMDs), and to evaluate their level of comfort in performing brush biopsies. METHODS: Participants were five DHs and five Ds who received one day of theoretical and clinical training in oral pathology to identify OPMDs (leukoplakia [LP], erythroplakia [EP], and oral lichen planus [OLP]), and perform brush sampling for PAP cytology and high-risk human papillomavirus (hrHPV) analysis. RESULTS: Out of 222 collected samples, 215 were adequate for morphological assessment and hrHPV analysis. All the participants agreed that sample collection can be incorporated in DHs and Ds routine clinical duties, and most of them reported that sample collection and processing was easy/quite easy. CONCLUSION: Dentists and DHs are capable of collecting satisfactory material for cytology and hrHPV analysis. All the participating DHs and Ds were of the opinion that brush sampling could be handled routinely by DHs and Ds in GDP.

Aerosol Retention Characteristics of Barrier Devices.

BACKGROUND: Disease severity in coronavirus disease 2019 (COVID-19) may be associated with inoculation dose. This has triggered interest in intubation barrier devices to block droplet exposure; however, aerosol protection with these devices is not known. This study hypothesized that barrier devices reduce aerosol outside of the barrier. METHODS: Aerosol containment in closed, semiclosed, semiopen, and open barrier devices was investigated: (1) "glove box" sealed with gloves and caudal drape, (2) "drape tent" with a drape placed over a frame, (3) "slit box" with armholes and caudal end covered by vinyl slit diaphragms, (4) original "aerosol box," (5) collapsible "interlocking box," (6) "simple drape" over the patient, and (7) "no barrier." Containment was investigated by (1) vapor instillation at manikin's right arm with video-assisted visual evaluation and (2) submicrometer ammonium sulfate aerosol particles ejected through the manikin's mouth with ventilation and coughs. Samples were taken from standardized locations inside and around the barriers using a particle counter and a mass spectrometer. Aerosol evacuation from the devices was measured using standard hospital suction, a surgical smoke evacuator, and a Shop-Vac. RESULTS: Vapor experiments demonstrated leakage via arm holes and edges. Only closed and semiclosed devices and the aerosol box reduced aerosol particle counts (median [25th, 75th percentile]) at the operator's mouth compared to no barrier (combined median 29 [-11, 56], n = 5 vs. 157 [151, 166], n = 5). The other barrier devices provided less reduction in particle counts (133 [128, 137], n = 5). Aerosol evacuation to baseline required 15 min with standard suction and the Shop-Vac and 5 min with a smoke evacuator. CONCLUSIONS: Barrier devices may reduce exposure to droplets and aerosol. With meticulous tucking, the glove box and drape tent can retain aerosol during airway management. Devices that are not fully enclosed may direct aerosol toward the laryngoscopist. Aerosol evacuation reduces aerosol content inside fully enclosed devices. Barrier devices must be used in conjunction with body-worn personal protective equipment.

High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden, Brazil and Romania.

OBJECTIVES: Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world. PATIENTS AND METHODS: A total of 432 patients with OL from Sweden, Brazil and Romania were analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A real-time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58 and 59, was performed to detect HR-HPV in patients with OL. RESULTS: In the Swedish and Romanian cohorts, none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours. CONCLUSIONS: In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.

Impact of a contactless prescription pickup kiosk on prescription abandonment, patient experience, and pharmacist consultations.

OBJECTIVE: Investigate the impact of increased access to new and refilled prescriptions by means of an automated pickup kiosk (Asteres ScriptCenter) on prescription abandonment rates, patient experience, and pharmacist consultations. DESIGN: Nonrandomized, observational study using retrospective, deidentified data from the filling pharmacy, the kiosk, and a pharmacist-completed counseling documentation log over a 35-month study period. SETTING AND PARTICIPANTS: Hospital employees opting to use a kiosk located in the lobby with 24 hours a day, 7 days a week access for pickups and a telephone pharmacist consultation service compared with employees using the regular counter at the filling pharmacy. OUTCOME MEASURES: Return to stock (RTS) rate to assess prescription abandonment, time to prescription pickup, consultation duration, kiosk user assessment, and pharmacist assessment of counseling ability. RESULTS: Approximately 9% of employees (440) enrolled to use the kiosk, with 5062 kiosk pickups recorded for new prescriptions (29%), refill prescriptions (33%), and over-the-counters (38%). The mean kiosk RTS (4.3% ± 3.2) was lower than that at the regular counter (5.6% ± 0.8), P = 0.04, whereas the mean time to pickup was approximately 1 day greater at the kiosk than the regular counter (2.8 ± 0.4 vs. 1.8 ± 0.2, P < 0.001). The average kiosk consultation was approximately 1 minute shorter (2.0 ± 1.4) than that of the regular counter (3.4 ± 1.9, P < 0.001), and fewer patients using the kiosk (15.7%) had additional questions at the end of a consultation session than patients at the regular counter (38.8%, P < 0.001). Most of the kiosk users agreed that their prescription questions were answered and that kiosk convenience was an important reason for using the filling pharmacy. Almost all (>90%) pharmacists indicated that they were able to effectively counsel patients at the kiosk and the regular counter. CONCLUSION: The kiosk, used by self-selected health care workers located in a hospital workplace setting with 24 hours a day, 7 days a week access, was a convenient, contactless pickup extension of the filling pharmacy with a lower prescription abandonment rate and similar pickup and consultation characteristics as at the regular pharmacy counter.

Patient-reported pain after surgical removal of leukoplakia - an observational 1-year follow-up study.

OBJECTIVE: Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. METHODS: Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. RESULTS: Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022). CONCLUSION: We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.

National survey of physicians' perspectives on pharmacogenetic testing in solid organ transplantation.

INTRODUCTION: Our objective was to evaluate physicians' perspectives on the clinical utility of pharmacogenetic (PGx) testing in kidney, liver, heart, and lung transplantation (KLHL-Tx). METHODS: A 36-question web-based survey was developed and administered to medical and surgical directors of US KLHL-Tx centers. RESULTS: There were 82 respondents (10% response rate). The majority were men (78%), non-Hispanic whites (70%), medical directors (72%), and kidney transplant physicians (35%). Although 78% of respondents reported having some PGx education, most reported lack of confidence in their PGx knowledge and ability to apply a PGx test. Participants reported mixed views about the clinical utility of PGx testing-most agreed with the efficacy of PGx testing, but not the benefits relative to the risks or standard of care. While 55% reported that testing was available at their institution, only 38% ordered a PGx test in the past year, most commonly thiopurine-S-methyltransferase. Physician-reported barriers to PGx implementation included uncertainty about the clinical value of PGx testing and patient financial burden. CONCLUSION: Together, our findings suggest prospective PGx research and pilot implementation programs are needed to elucidate the clinical utility and value of PGx in KLHL-Tx. These initiatives should include educational efforts to inform the use of PGx testing.

Improved Glycemic Control Outcomes Regardless of Mental Health Disorders in a Pharmacist-Endocrinologist Diabetes Intense Medical Management (DIMM) "Tune Up" Clinic.

Background: Previous studies show patients with type 2 diabetes (T2D) and a mental health (MH) disorder exhibit poorer glycemic control compared with those without. Objective: Compare mean change in glycosylated hemoglobin (A1C) after 6 months in the Diabetes Intense Medical Management (DIMM) "Tune Up" Clinic in patients with and without MH disorders. Methods: Retrospective cohort study in T2D patients, with A1C at baseline and 6 months, divided into subgroups of those with ≥1 MH diagnoses and without MH. Primary outcome was mean change in A1C from baseline to 6 months. Secondary outcomes were mean change in other metabolic parameters and proportion achieving A1C and related goals. Results: Of 155 patients meeting inclusion criteria, 66 (42.6%) had at least 1 MH disorder (MH group) and 89 (57.4%) did not (non-MH group). Mean A1C, fasting blood glucose (FBG), and triglycerides (TG) change (improvement) did not differ significantly between MH and non-MH groups at 6 months (eg, A1C reduction: -2.1% [SD = 2.0] vs -2.3% [SD = 2.1]; P = 0.61, respectively). Percentage at A1C goal did not differ significantly between groups, though a higher percentage of the non-MH group achieved FBG and TG goals than the MH group. Conclusion and Relevance: In 6 months, both groups in the DIMM clinic achieved a statistically significant mean A1C reduction (over 2%) with no statistical or clinical difference in the magnitude of change between groups. Patients with T2D benefitted from the DIMM model and personalized visits with a pharmacist regardless of having a MH disorder.

PaCIR: A tool to enhance pharmacist patient care intervention reporting.

OBJECTIVES: To develop a pharmacist patient care services intervention reporting checklist to be used in conjunction with existing primary reporting tools. The tool should enhance consistent reporting of pharmacist patient care interventions. Tool use in pharmacist-patient care intervention reporting may increase: (1) likelihood for inclusion in higher order analyses and (2) successful replication. METHODS: Adhering to principles of the Equator Network, a modified Delphi approach was used. An expert group identified guidance need, conducted a thorough literature search confirming need, developed a comprehensive list of potential elements, refined the list via multiple rounds, finalized language and structure, and published the checklist. Multiple rounds of iterative input were completed face to face, in conference calls, and during public comment periods. The finalized list of elements was organized into a logical flow with the use of clear and concise language and then transformed into an intuitive checklist. RESULTS: The core task force identified 9 critical components over a 4-year period Collectively, the input represented more than 200 stakeholders. Stakeholders overwhelmingly supported the inclusion (89%; n = 29) and clarity (91%; n = 26) of each element. The final 9 elements were organized into a checklist to enhance pharmacist patient care intervention reporting (PaCIR). Accompanying each element is a specific explanation justifying its inclusion. An appendix containing published and created examples of how authors may satisfactorily meet each element is provided. CONCLUSION: Use of the PaCIR checklist will enhance the quality of reporting of pharmacist patient care intervention studies. This enhanced quality can support replication of the studies and increase the likelihood these studies will be considered for inclusion in systematic reviews and meta-analyses. Researchers are urged to consider use of reporting guides such as PaCIR during the project design phase.

Improved Glycemic Control With Minimal Change in Medication Regimen Complexity in a Pharmacist-Endocrinologist Diabetes Intense Medical Management (DIMM) "Tune Up" Clinic.

BACKGROUND: Gaining glycemic control in patients with type 2 diabetes (T2D) usually requires more complicated medication regimens. Increased medication regimen complexity (MRC) negatively impacts adherence and clinical outcomes. OBJECTIVE: Compare MRC change in patients with uncontrolled T2D referred to a collaborative pharmacist-endocrinologist Diabetes Intense Medical Management (DIMM) clinic "tune up" model versus similar patients receiving usual primary care provider (PCP) care over 6 months. METHODS: Retrospective, observational, comparative cohort study compared MRC of complex DIMM clinic patients to a similar group (adults with T2D, glycosylated hemoglobin [A1C] ≥8%), continuing to receive usual care from their PCPs. The MRC Index (MRCI) was used to quantify MRC. RESULTS: Both DIMM (n=99) and PCP (n=56) groups were similar, with high baseline mean MRC scores as measured by number of medications and MRCI (12.0 [SD=5.7] vs 13.7 [SD = 5.6], and 32.7 [SD=17.0] vs 38 [SD=16.5]), respectively. Mean MRC change over 6 months was not significantly different between groups, although mean A1C reduction was significantly greater in the DIMM versus PCP group (-2.4% [SD=2.1] vs -0.8% [SD=1.7], P<0.001, respectively). CONCLUSIONS AND RELEVANCE: Outcomes represent the first report demonstrating how treating patients with an innovative DIMM model can help complex T2D patients achieve glycemic control without increasing the MRC to more than a comparator group. With the growing prevalence of T2D and associated elevated treatment costs, identifying effective means for achieving glycemic control without increasing complexity is needed. Application of this model may be considered by other health systems to aid in achieving outcome measures.

Cost of Prescription Drug-Related Morbidity and Mortality.

BACKGROUND: Public attention and recent US Congressional activity has intensified focus on escalating medication prices. However, the actual cost of medication use extends beyond the up-front cost of purchasing medicines. It also encompasses the additional medical costs of morbidity and mortality resulting from nonoptimized medication regimens, including medication nonadherence. OBJECTIVES: Applying the most current nationally representative data sources, our goal was to estimate the cost of prescription drug-related morbidity and mortality in the United States. METHODS: Total costs of nonoptimized prescription drug use and average pathway costs for a patient who experienced a treatment failure (TF), a new medical problem (NMP), or a TF and NMP were modeled in Microsoft Excel (Microsoft Corporation, Redmond, WA) and TreeAge Pro Healthcare, v2014 (TreeAge Software, Inc, Williamstown, MA), respectively. RESULTS: The estimated annual cost of prescription drug-related morbidity and mortality resulting from nonoptimized medication therapy was $528.4 billion in 2016 US dollars, with a plausible range of $495.3 billion to $672.7 billion. The average cost of an individual experiencing TF, NMP, or TF and NMP after initial prescription use were $2481 (range: $2233, $2742), $2610 (range: $2374, $2848) and $2572 (range: $2408, $2751), respectively. CONCLUSIONS: The estimated annual cost of drug-related morbidity and mortality resulting from nonoptimized medication therapy was $528.4 billion, equivalent to 16% of total US health care expenditures in 2016. We propose expansion of comprehensive medication management programs by clinical pharmacists in collaborative practices with physicians and other prescribers as an effective and scalable approach to mitigate these avoidable costs and improve patient outcomes.

Medication Regimen Complexity in Long-Term Care Facilities and Adverse Drug Events-Related Hospitalizations.

Adverse drug events (ADE) are a leading cause of mortality in the United States. Recent studies have demonstrated a high level of complex medication regimens in institutionalized residents. Evidence of the relationship between medication regimen complexity (MRC) and ADE-related rehospitalizations or emergency department (ED) visits is evolving. Therefore, there is a demand for better characterization and study of MRC as an objective identifier to quickly screen and prioritize high-risk patients for follow-up medication management therapy. This manuscript will serve as a brief summary review of the current findings regarding the relationship between MRC and hospital readmission and ED usage and provide strategies for pharmacists to more efficiently evaluate complex medication regimens and optimize therapies.

Perioperative cerebrospinal fluid and plasma inflammatory markers after orthopedic surgery.

BACKGROUND: Postoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid (CSF) even after aseptic surgery, suggesting that inflammation of the central nervous system may be part of the pathogenesis of postoperative cognitive changes. We investigated the hypothesis that neuroinflammation was an important cause for postoperative delirium and cognitive dysfunction after major non-cardiac surgery. METHODS: After Institutional Review Board approval and informed consent, we recruited patients undergoing major knee surgery who received spinal anesthesia and femoral nerve block with intravenous sedation. All patients had an indwelling spinal catheter placed at the time of spinal anesthesia that was left in place for up to 24 h. Plasma and CSF samples were collected preoperatively and at 3, 6, and 18 h postoperatively. Cytokine levels were measured using ELISA and Luminex. Postoperative delirium was determined using the confusion assessment method, and cognitive dysfunction was measured using validated cognitive tests (word list, verbal fluency test, digit symbol test). RESULTS: Ten patients with complete datasets were included. One patient developed postoperative delirium, and six patients developed postoperative cognitive dysfunction. Postoperatively, at different time points, statistically significant changes compared to baseline were present in IL-5, IL-6, I-8, IL-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, IL-6/IL-10, and receptor for advanced glycation end products in plasma and in IFN-γ, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1ß, IL-8/IL-10, and TNF-α in CSF. CONCLUSIONS: Substantial pro- and anti-inflammatory activity in the central neural system after surgery was found. If confirmed by larger studies, persistent changes in cytokine levels may serve as biomarkers for novel clinical trials.

Clinical Outcomes Associated With a Collaborative Pharmacist-Endocrinologist Diabetes Intense Medical Management "Tune Up" Clinic in Complex Patients.

BACKGROUND: No previous studies exist examining the impact of a short-term pharmacist-endocrinologist collaborative practice model on glycemic control in complex patients. OBJECTIVE: Evaluate outcomes associated with a PharmD-Endocrinologist Diabetes Intense Medical Management (DIMM) "tune up" clinic for complex patients. METHODS: A retrospective cohort study of 99 patients referred to DIMM clinic versus a comparator group of 56 primary care provider (PCP) patients meeting the same criteria (adult type 2 diabetes patients, glycosylated hemoglobin [A1C] ≥ 8%, follow-up visit within 6 months) in a Veterans Affairs Medical Center. DIMM clinic used a short-term model that coupled personalized clinical care with real-time, patient-specific diabetes education during two to four 60-minute visits over 6 months. PCP patients received usual care. Primary outcome was mean A1C change after 6 months. Secondary measures included fasting blood glucose, lipids, blood pressure, weight, body mass index, and percentage of patients meeting goals. RESULTS: Patients in each group had an average of 8 and were taking 12 to 14 medications daily. Mean A1C (%) improvement in DIMM group was significantly greater at 6 months (-2.4 [SD = 2.1] vs -0.8 [SD = 1.7]; P < 0.001), than PCP group. Percentage meeting A1C goal levels (<7%, <8%, and <9%) was significantly greater at 3 and 6 months compared with baseline in the DIMM group (P < 0.001) versus (only <8%) at 3 and 6 months compared with baseline in PCP group. CONCLUSIONS: The DIMM clinic "tune up" model demonstrates a successful collaborative practice which helped complex diabetes patients achieve glycemic control in a 6-month period.

Clinical, Morphological, and Molecular Evaluations of Bone Regeneration With an Additive Manufactured Osteosynthesis Plate.

There is limited information on the biological status of bone regenerated with microvascular fibula flap combined with biomaterials. This paper describes the clinical, histological, ultrastructural, and molecular picture of bone regenerated with patient-customized plate, used for mandibular reconstruction in combination with microvascular osteomyocutaneous fibula flap. The plate was virtually planned and additively manufactured using electron beam melting. This plate was retrieved from the patient after 33 months. Microcomputed tomography, backscattered-scanning electron microscopy, histology, and quantitative-polymerase chain reaction were employed to evaluate the regenerated bone and the flap bone associated with the retrieved plate. At retrieval, the posterior two-thirds of the plate were in close adaptation with the underlying flap, whereas soft tissue was observed between the native mandible and the anterior one-third. The histological and structural analyses showed new bone regeneration, ingrowth, and osseointegration of the posterior two-thirds. The histological observations were supported by the gene expression analysis showing higher expression of bone formation and remodeling genes under the posterior two-thirds compared with the anterior one-third of the plate. The observation of osteocytes in the flap indicated its viability. The present data endorse the suitability of the customized, additively manufactured plate for the vascularized fibula mandibular reconstruction. Furthermore, the combination of the analytical techniques provides possibilities to deduce the structural and molecular characteristics of bone regenerated using this procedure.

Nested PCR for detection of HSV-1 in oral mucosa.

BACKGROUND: It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing. RESULTS: HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant. CONCLUSIONS: We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected.

Patient-Level Medication Regimen Complexity in Patients With HIV.

BACKGROUND: Patients with HIV often have multiple medications besides antiretrovirals (ARV). Medication regimen complexity-formulations, dosing frequencies, and additional directions-expands pill burden by considering self-care demands. Studies show an inverse association between ARV adherence and medication complexity for ARVs only. Patient-level medication regimen complexity beyond ARV complexity is unknown. OBJECTIVE: To measure and characterize Patient-level Medication Regimen Complexity Index (pMRCI) and Antiretroviral Medication Regimen Complexity Index (ARCI) for patients in 2 HIV clinics. We hypothesized that an all-medication complexity metric will exceed disease-state-defined complexity metrics; for ARVs only, the pMRCI score will be smaller than the ARCI score by capturing fewer features of regimens. Associations between complexity and adherence were not assessed. METHOD: Electronic records supplied a retrospective, random sample of adult patients with HIV; medication lists were used to code the pMRCI (n=200). A random subsample (n=66) was coded using ARCI for ARV regimens only. RESULT: Medication counts ranged from 1 to 27; pMRCI scores ranged from 2 to 67.5. ARVs contributed roughly 25% to the pMRCI; other prescriptions contributed about 66%. Dosing frequency made the largest contribution of all components (62%) to the pMRCI. For ARVs, pMRCI and ARCI scores did not differ statistically. CONCLUSION: Unique dosing frequencies raised complexity and may provide opportunities for intervention. Other prescriptions drove pMRCI scores, suggesting that HIV management programs should review all medications. A patient-level approach added value to understanding the role of medications in patient complexity; future work can assess association of pMRCI with adherence and patient outcomes.

Double impact of cigarette smoke and mechanical ventilation on the alveolar epithelial type II cell.

INTRODUCTION: Ventilator-induced lung injury (VILI) impacts clinical outcomes in acute respiratory distress syndrome (ARDS), which is characterized by neutrophil-mediated inflammation and loss of alveolar barrier function. Recent epidemiological studies suggest that smoking may be a risk factor for the development of ARDS. Because alveolar type II cells are central to maintaining the alveolar epithelial barrier during oxidative stress, mediated in part by neutrophilic inflammation and mechanical ventilation, we hypothesized that exposure to cigarette smoke and mechanical strain have interactive effects leading to the activation of and damage to alveolar type II cells. METHODS: To determine if cigarette smoke increases susceptibility to VILI in vivo, a clinically relevant rat model was established. Rats were exposed to three research cigarettes per day for two weeks. After this period, some rats were mechanically ventilated for 4 hours. Bronchoalveolar lavage (BAL) and differential cell count was done and alveolar type II cells were isolated. Proteomic analysis was performed on the isolated alveolar type II cells to discover alterations in cellular pathways at the protein level that might contribute to injury. Effects on levels of proteins in pathways associated with innate immunity, oxidative stress and apoptosis were evaluated in alveolar type II cell lysates by enzyme-linked immunosorbent assay. Statistical comparisons were performed by t-tests, and the results were corrected for multiple comparisons using the false discovery rate. RESULTS: Tobacco smoke exposure increased airspace neutrophil influx in response to mechanical ventilation. The combined exposure to cigarette smoke and mechanical ventilation significantly increased BAL neutrophil count and protein content. Neutrophils were significantly higher after smoke exposure and ventilation than after ventilation alone. DNA fragments were significantly elevated in alveolar type II cells. Smoke exposure did not significantly alter other protein-level markers of cell activation, including Toll-like receptor 4; caspases 3, 8 and 9; and heat shock protein 70. CONCLUSIONS: Cigarette smoke exposure may impact ventilator-associated alveolar epithelial injury by augmenting neutrophil influx. We found that cigarette smoke had less effect on other pathways previously associated with VILI, including innate immunity, oxidative stress and apoptosis.

Early Detection of Oral Potentially Malignant Disorders: A Review on Prospective Screening Methods with Regard to Global Challenges.

Oral cancer is a cancer type that is widely prevalent in low-and middle-income countries with a high mortality rate, and poor quality of life for patients after treatment. Early treatment of cancer increases patient survival, improves quality of life and results in less morbidity and a better prognosis. To reach this goal, early detection of malignancies using technologies that can be used in remote and low resource areas is desirable. Such technologies should be affordable, accurate, and easy to use and interpret. This review surveys different technologies that have the potentials of implementation in primary health and general dental practice, considering global perspectives and with a focus on the population in India, where oral cancer is highly prevalent. The technologies reviewed include both sample-based methods, such as saliva and blood analysis and brush biopsy, and more direct screening of the oral cavity including fluorescence, Raman techniques, and optical coherence tomography. Digitalisation, followed by automated artificial intelligence based analysis, are key elements in facilitating wide access to these technologies, to non-specialist personnel and in rural areas, increasing quality and objectivity of the analysis while simultaneously reducing the labour and need for highly trained specialists.